#1

What do people think of this article, any criticism?
I don’t know enough personally to determine what to prioritize.

Feel free to post other articles on the topic and adjacent to it.

#2

“Aging, an overloaded term, here means adult biological aging, not childhood development nor just time passing. Semantics is the root of much of the disagreement but should be irrelevant”

This is a pretty good point. I don’t think any of us would argue that a baby aging to a teenager is a disease process. There reaches a peak, and then a decline, and this is where we need to differentiate.

This sort of reminds me of the discussion of “steroids”, and testosterone/TRT being lumped in with other steroids. When we really mean performance enhancing drugs, not steroids. Clenbuterol, a non-steroidal fat burner, is included in this false classification. Bugs the hell out of me.

“Adult biological aging consists of several interacting but distinct pathological molecular processes.”

Seems we are circling back to the hallmarks of aging. It does seem to be the best model, but we need more data on each one to properly treat them. I also agree with the Aubrey de Grey approach of fixing damage ASAP without waiting until we understand the vast complex metabolic processes behind them.

" Classifying aging as a disease would immediately speed clinical trials . This is too simplistic; human lifespan studies are too long and expensive, and we don’t yet have biomarkers trustworthy enough to be surrogate endpoints. Focusing on subpathologies of aging might help here."

Calling it simplistic misses the point that the classification would speed up the necessary prerequisites of reaching those clinical trials. Better biomarkers and aging clocks will allow more effective human clinical trials. Better trial methods such as testing on printed human organs, cloned humans or in silico could supercharge data acquisition.

All of this will be accelerated by the acceptance that aging is a disease. Or something even more important than a disease.

" Labeling aging a disease could cause stress/depression ."

This is also obviously meaningless. We will find ways to cope with this. All of us here have found ways of coping with this. You cope by taking positive constructive action towards a solution. Nothing would make me more confident than a species wide all out war on aging.

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#3

Looking at his summary:

First, this is the wrong question. The right question is what regulatory framework optimizes long term health? Second, aging isn’t one thing, but multiple distinct pathological processes. Third, there were analogous debates on obesity – it wasn’t a disease but now is. A new proposal to distinguish clinical obesity could be copied.

He is right that a key question is the regulatory environment and to what it extent it hinders or helps the safe production of interventions that act to constrain age related diseases in the round by intervening in the aging pathway.

Increasing the amount of regulation on “anti-aging” interventions - which is the main effect of classifying aging as a disease - in my personal view will hold back progress.

I think he is wrong to say:

Second, aging isn’t one thing, but multiple distinct pathological processes.

However, on the underlying thesis I think he is wrong in principle as we have enough problems as it stands with the interplay between regulation and progress and making it more complicated would not help.

I posted separately about the FDA and gene therapy on one issue which does demonstrate the complexities in terms of medical regulation.

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#4

Regarding not classifying the body as aging while it is still in the development stage (growing) - I frequently think about how to regard edge cases. One such is the case of some breeds of giant dogs. Those dogs age at an accelerated rate. Frequently they will display signs of aging in many tissues very early, like the heart and CV system, gray hair on the muzzle and the like, but yet have not completed their growth in bone and musculature as they are reaching maturity. So you have a case of simultaneous development and decline of disparate tissues. This is in contrast to the usual assumption of growth until maturity and subsequent decline of aging. I think tissues organs and systems simply do not age uniformly in any case, it’s just more extreme and readily observable in cases like that of the giant dog breeds. There is an interesting discussion to be had about establishing the point of maturity, which frequently is pegged to reproductive capacity. Reaching sexual maturity completes some aspects of development, but not necessarily all. It’s also highly species specific. You have many organisms that reach the reproductive stage and die immediately, sometimes in the very act of reproduction - essentially there is no aging as there’s no time - it’s developed immediately followed by death, skipping the whole aging process. At the other extreme you have some species of crustaceans that also skip aging by essentially being stuck in the development stage by endless growing (they die as a result of incomplete molting, when they become too big to complete the molting process, or else predation).

I think aging can essentially be reduced to cellular senescence. That’s aging in a microcosm. You avoid classifying systems or even tissue level senescence thus simplifying any argument about aging on the level of a whole organism and getting into the weeds of disparate aging rates. The individual cell can have a distinct senescent profile that can be classified. At that point you can say that there’s the aging process associated with those changes. That is the aging process which then translates to tissue level changes in an aging phenotype cascade.

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#5

My view is that Aging and Development are the same process all driven by acetylation shifts. In particular development is I think driven by acetylation shifts mainly in splicing factors. When it comes to puberty it is splicing changes that drive hormonal changes.

ΔΨM → C₆H₈O₇ → C23H38N7O17P3S → Splicing Shifts

Separately SASP inhibits SLC25A1 thereby reducing C₆H₈O₇

#6

Calling it a disease is really just about classification, I don’t think it has anything to do with the actual ‘science’. We just need a way to allow aging to be classified as a disease to allow geroscience interventions to move into the clinic.

My theory is that aging is really just the breakdown of an incredibly complex system designed to be resilient enough to reproduce and pass on genes within a particular environmental niche.

Because of the system’s complexity there are multiple points of failure and interconnected feedback loops, which is why I believe looking for a specific cause is reductionist and won’t get us anywhere. at best I think all we’re doing a moment is noodling around the edges.

When you’re dealing with this level of complexity, breakdowns happen through cascading failures across multiple pathways simultaneously.

I think it’s why most interventions fall short, because there’s no single point of failure, it’s the deterioration of an entire network operating beyond its evolutionary design parameters. I think the only way to meaningfully address aging is to figure out how to improve the system’s overall resilience, essentially upgrading its architecture rather than trying to fix individual breakdowns.

Altos Labs are doing some really interesting work on engineering stem cells, which I think is the direction we should be going in.

https://www.sciencedirect.com/science/article/abs/pii/S0092867425005719

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#7

It’s all about regulation. Regulation is a complex issue, but it adds costs to a development process. It can stop people trying to do things as the regulatory cost is potentially very high compared to any return. This, of course, depends upon what intellectual property is available against any investment.

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#8

Absolutely, and regulation is a huge bottle neck to progress, but it’s also necessary. I think though, the science is accelerating and the regulation isn’t fit for purpose anymore.

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#9

I think there are issues as to the nature of the evidence required to make claims. From a safety perspective I think things are essentially OK as there are things which are known to be safe, but there are limits as to what can be said about them.

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